Biomolecular engineers developed versatile antibodies to solve reverse inflammatory diseases

In the picture: 3D models of an engineered antibody (grey) able to bind multiple chemokines (other colors)

Scientists at the Massachusetts Institute of Technology, Harvard Medical School and Ca’ Foscari University of Venice have developed a new generation of antibodies that reversed chronic inflammation and improved disease outcome more effectively than traditional therapies according to early tests. The result was published today on the scientific journal Nature Communications.

The ELR+ CXC chemokines are proteins that have a prominent role in the development of numerous inflammatory diseases and are attractive therapeutic targets. Antibodies capable of blocking one chemokine at a time have proved insufficient to provide beneficial effects. By applying principles of darwinian evolution to proteins in the laboratory, scientists have isolated antibodies able to recognize more than ten different chemokines.

“Our immune system can generate a virtually unlimited repertoire of antibodies able to recognize a large variety of molecular structures named “antigens” - explained Alessandro Angelini, researcher at the Department of Molecular Sciences and Nanosystems at Ca’ Foscari University of Venice and professor at the new PhD programme in Science and Technology of Bio and Nanomaterials. However this process is highly selective: an antibody usually recognize only one antigen at a time. To develop a single therapeutic antibody able to neutralize multiple antigens concomitantly we had to employ advanced protein engineering techniques”.

Using yeast and combinatorial tools, scientists successfully created antibodies that are able to bind human and murine chemokines. Once tested in a mouse model for arthritis, these antibodies demonstrated greater therapeutic efficacy than traditional molecules, confirming that blocking of multiple chemokines at a time is required to prevent and resolve the disease.

These molecules are the result of five years of work and are now available to the scientific community for further studies.

This novel strategy was used to engineer multispecific antibodies against ELR+ CXC chemokines but this study has value as a proof-of-concept for a general approach that could be applied to other therapeutic interventions involving multiple protein targets such as as cancer and autoimmune diseases.

Enrico Costa